Feasibility of Identifying Pancreatic Cancer Based on Serum Metabolomics
Feasibility of Identifying Pancreatic Cancer Based on Serum Metabolomics
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DOI：
10.1158/1055-9965.epi-10-0712
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发表时间：
2011-01-01
影响因子：
3.8
通讯作者：
Vogel, Hans J.
中科院分区：
文献类型：
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作者：
Bathe, Oliver F.;Shaykhutdinov, Rustem;Vogel, Hans J.
背景：我们假设血液中各种代谢物的丰度将有助于胰腺和胆道病变的诊断，这可能会避免不必要的手术。方法：对43例良性肝胆疾病患者（n = 43）和56例胰腺癌患者（n = 56）的血清样本进行(1)核磁共振（H NMR）检测，定量鉴定58种独特代谢物。数据通过“目标分析”进行分析，然后进行监督模式识别和最显著代谢物的正交偏最小二乘判别分析（O-PLS-DA），从而可以在组间比较整个样本光谱。结果：胰腺癌患者的代谢组学谱与良性疾病患者有显著差异（AUROC， ROC曲线下面积，= 0.8372）。显性糖尿病（DM）被认为是胰腺癌组的一个可能的混杂因素。因此，糖尿病患者被排除在进一步的分析之外。多变量分析显示，在这一更为均匀的胰腺癌组中，与良性病例相比，血清谷氨酸和葡萄糖浓度升高最多。在良性病例中，肌酸和谷氨酰胺含量最高。为了检验该测试的有效性，对年龄和性别匹配的良性病变模拟癌症的对照组进行了比较，也控制了黄疸和糖尿病的存在（每组n = 14）。胰腺癌患者的代谢谱与胰腺良性病变患者的代谢谱仍然存在差异（AUROC = 0.8308）。结论：血清代谢组学特征可用于区分胰腺良恶性病变。影响：需要进一步研究黄疸和糖尿病的影响。将使用质谱法评估更全面的代谢组学概况。癌症流行病学生物标志物；20 (1);140 - 7。(c) 2010年aacr。
Background: We postulated that the abundance of various metabolites in blood would facilitate the diagnosis of pancreatic and biliary lesions, which could potentially prevent unnecessary surgery.Methods: Serum samples from patients with benign hepatobiliary disease (n = 43) and from patients with pancreatic cancer (n = 56) were examined by (1)H NMR spectroscopy to quantify 58 unique metabolites. Data were analyzed by "targeted profiling" followed by supervised pattern recognition and orthogonal partial least-squares discriminant analysis (O-PLS-DA) of the most significant metabolites, which enables comparison of the whole sample spectrum between groups.Results: The metabolomic profile of patients with pancreatic cancer was significantly different from that of patients with benign disease (AUROC, area under the ROC curve, = 0.8372). Overt diabetes mellitus (DM) was identified as a possible confounding factor in the pancreatic cancer group. Thus, diabetics were excluded from further analysis. In this more homogeneous pancreatic cancer group, compared with benign cases, serum concentrations of glutamate and glucose were most elevated on multivariate analysis. In benign cases, creatine and glutamine were most abundant. To examine the usefulness of this test, a comparison was made to age-and gender-matched controls with benign lesions that mimic cancer, controlling also for presence of jaundice and diabetes (n = 14 per group). The metabolic profile in patients with pancreatic cancer remained distinguishable from patients with benign pancreatic lesions (AUROC = 0.8308).Conclusions: The serum metabolomic profile may be useful for distinguishing benign from malignant pancreatic lesions.Impact: Further studies will be required to study the effects of jaundice and diabetes. A more comprehensive metabolomic profile will be evaluated using mass spectrometry. Cancer Epidemiol Biomarkers Prev; 20(1); 140-7. (C) 2010 AACR.